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NIH grant 1R01AR087742-01: Mechanisms of systemic bone loss following fracture
Institute: {'code': 'AR', 'abbreviation': 'NIAMS', 'name': 'National Institute of Arthritis and Musculoskeletal and Skin Diseases', 'admin_org_id': '12500006', 'admin_funding_url': ''}. PI: Blaine A. Christiansen. Award: $448563.
Start: 2026-09-05T00:00:00.
PROJECT SUMMARY/ABSTRACT
Osteoporosis and low bone mass affect over 50 million Americans, and osteoporosis-related fractures account
for over three million broken bones and $25 billion in related costs annually in the US. Identifying the underlying
causes of bone loss is therefore of utmost importance for improving the skeletal health of a rapidly aging
population. One underappreciated mechanism of bone loss is that fracture initiates post-traumatic bone loss
throughout the skeleton, which increases future fracture risk at all skeletal sites. Injury-induced inflammation
following fracture is a likely contributor to post-traumatic systemic bone loss. However, multiple other unidentified
biological processes may also contribute to systemic bone loss following fracture. Therefore, it is necessary to
develop a more holistic understanding of physiological processes initiated by injury and their effects on the
skeletal system. The parent R01 is an ongoing longitudinal study that uses clinical and cutting-edge high-
resolution imaging to characterize the time course and magnitude of systemic bone loss and recovery following
humerus fracture. For this ancillary study, we propose to collect additional blood from fracture patients at multiple
time points post-injury to perform an extensive unbiased multimodal analysis of circulating cells and factors
utilizing genomic, proteomic, and metabolomic profiling techniques. We will first perform: 1) single-cell RNAseq
of circulating leukocytes and osteoclast precursors to determine gene expression at the level of individual cells,
2) proteomic analysis of serum samples to determine whole-tissue protein expression, and 3) metabolomic
analysis of serum samples to determine small molecules (metabolites) present in blood at various time points
following fracture. Next, we will use multimodal predictive modeling to identify key biomarkers and mechanisms
driving post-fracture systemic bone loss, which will allow us to identify novel processes and develop a holistic
understanding of the injury response and individual effects on post-fracture systemic bone loss. These novel
studies will be highly impactful as they will: 1) reveal the inflammatory landscape initiated by fracture and
correlate this response to the magnitude of post-traumatic systemic bone loss and recovery, 2) identify novel
pathways initiated by fracture that may contribute to the systemic bone loss response, and 3) generate new
biomarkers and potential therapeutic targets for preserving skeletal health in older patients following a bone
fracture. This multimodal unbiased analysis of circulating cells and factors will add an unparalleled level of
investigative power to the parent R01 and will allow us to expand these studies toward deeper mechanistic
understanding and greater translational potential.document fetched 2026-09-13 02:45